A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Oxazole,pyrazole and piperidine derivatives having an o-hydroxyaryl moiety with anticipated molluscicidal activity

The condensation reactions of hippuric acid and its furyl derivative with salicylaldehydes or that of salicylhippuric acid analogues with furaldehyde led to the corresponding oxazoles. These were subsequently treated with hydrazine hydrate, hydroxylamine or subjected to alkaline hydrolysis to yield new o-hydroxyaryl or salicyl containing derivatives. 5-Substituted salicylanilides were treated with piperidine and formaldehyde in a Mannich type reaction affording the corresponding 3-(N-piperidinomethyl) salicylanilides. It was noticed that the presence of an electron donating group in position 3 in the salicylanilide moiety decreases the molluscicidal activity.     

Lessons not learned from the generalist initiatives.

The grouping of the primary care specialties (general internal medicine, general pediatrics, and family medicine) for research purposes is at best limiting the value of the information that is found and, at worst, leading researchers to erroneous conclusions. For example, three large studies each showed differences in abilities to predict students' specialty choices in primary care (e.g., in one study, the investigators correctly predicted 3% of those choosing general internal medicine, 29% considering general pediatrics, and 51% considering family medicine). These and related findings suggest that medical students entering the three primary care specialties are not a homogeneous group. While there were some factors predictive for all primary care specialties, there were more factors that were unique to the individual specialties Grouping the specialties may not reveal factors that are significantly related to only one of the specialties. In addition, when a variable operates in different ways for different specialties, findings where the specialties are combined can show a reduced effect of that variable or even no effect, because the directions of effects cancel each other. Researchers can fruitfully examine the primary care specialties as a group but at the same time report their data for the individual specialties, which would greatly increase our knowledge both of primary care and also about the similarities and dissimilarities of its component specialties. However, the best models continue to be either research in which the sample size is large enough to compare specialty groups statistically or research with a focus on just one of the primary care specialties.     

Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy

BackgroundRelapse remains a critical challenge in children with acute lymphoblastic leukemia (ALL). The emergence of immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs), and T regulatory (T_reg) cells, has been considered one potential mechanism of relapse in children with ALL.AimThis study aimed to address the microRNAs (miRNAs) related to MDSCs and T_reg cells and to explore their targeted immunoregulatory pathways.MethodsAffymetrix microarray was used for global miRNA profiling in B-ALL pediatric patients before, during, and after induction of chemotherapy. Bioinformatics analysis was performed on MDSCs and T_reg cells-related dysregulated miRNAs, and miR-Pathway analysis was performed to explore their targeted immunoregulatory pathways.Results516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Among them, 13 miRNAs and 8 miRNAs related to MDSCs and T_reg cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and T_reg cells; 4 of them were common in all patients. Four immune-related pathways; TNF, TGF-β, FoxO, and Hippo were found implicated.ConclusionOur pilot study concluded certain miRNAs related to MDSCs and T_reg cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.     

Histological,histochemical, and immunohistochemical studies of hippocampus in male New Zealand rabbits

The present study aims to give detailed histomorphological features of the hippocampus of adult male New Zealand rabbits. Both histological and histochemical specimens were prepared to be examined microscopically by using a light microscope. The hippocampus appeared as C-shaped hippocampal proper, dentate gyrus, and subiculum. The hippocampal proper subdivided along its length according to the density and size of its major constituent pyramidal cells into four distinct regions named Cornu Ammonis (CA1, CA2, CA3, and CA4). With the histochemical preparations, each of these regions consisted of five layers, stratum alveolus, stratum oriens, stratum pyramidale, stratum radiatum, and stratum lacunosum-moleculare. The stratum pyramidale constituted the middle dark zone and contained the principal excitatory neurons and a few interneurons. Histochemically, the pyramidal neurons along all regions of the CA reacted positively to Grimelius silver impregnation, lead hematoxylin, Gomori's aldehyde fuchsin, aldehyde thionine, Gomori's chrome alum hematoxylin, and performic acid alcian blue stains. Immunohistochemically, the pyramidal neurons reacted positively to anti-NSE antibodies. The dentate gyrus was formed of three distinct layers. The subiculum was formed of proper subiculum, presubiculum, and parasubiculum.     

Study of the Rectal Electric Activity of the Uninhibited Rectal Detrusor (Overactive Rectum): A New Concept of Pathogenesis

Abstract

Background/Objective: One of the causes of fecal incontinence is uninhibited rectal detrusor syndrome (URDS). Patients with this condition either perceived the first rectal sensation after the onset of involuntary rectal contraction or not at all. We investigated the hypothesis that the abnormal rectal contractility in URDS may be caused by deranged rectal electric activity.

Methods: Twenty-five patients with URD (14 women and 11 men; age, 44.7 ± 10.3 years) and 10 healthy volunteers (6 women and 4 men; age, 42.8 ± 8.7 years) were studied. URDS was diagnosed by rectometry and provocative test. A transcutaneous EMG was performed with one electrode placed lateral to each sacroiliac joint and the third one midway between the greater trochanter and the ischial tuberosity. Two 20- minute recording sessions were performed for each subject.

Results: Slow waves (SWs) with regular rhythm and similar parameters (frequency, amplitude, conduction velocity) from the 3 electrodes were recorded from the healthy volunteers. They showed a significant increase in the parameters on saline filling of the rectum. The SWs of patients with URDS exhibited a “dysrhythmic” pattern with irregular parameters, which were different in the 3 electrodes and inconsistent during recording. They showed areas of tachyrhythmia, bradyrhythmia, and arrhythmia. On provoking rectal overactivity, the SWs showed an increased dysrhythmic activity.

Conclusions: The patients with URD exhibited a “dysrhythmic” electric pattern with areas of variable electric activity. The tachyrhythmic areas seem to initiate the urgency and fecal incontinence of URDS. It is suggested that a disordered rectosigmoid pacemaker causes the dysrhythmic waves.     

Indirect Treatment Comparison/Network Meta-Analysis Study Questionnaire to Assess Relevance and Credibility to Inform Health Care Decision Making: An ISPOR-AMCP-NPC Good Practice Task Force Report

Despite the great realized or potential value of network meta-analysis of randomized controlled trial evidence to inform health care decision making, many decision makers might not be familiar with these techniques. The Task Force developed a consensus-based 26-item questionnaire to help decision makers assess the relevance and credibility of indirect treatment comparisons and network meta-analysis to help inform health care decision making. The relevance domain of the questionnaire (4 questions) calls for assessments about the applicability of network meta-analysis results to the setting of interest to the decision maker. The remaining 22 questions belong to an overall credibility domain and pertain to assessments about whether the network meta-analysis results provide a valid answer to the question they are designed to answer by examining 1) the used evidence base, 2) analysis methods, 3) reporting quality and transparency, 4) interpretation of findings, and 5) conflicts of interest. The questionnaire aims to help readers of network meta-analysis opine about their confidence in the credibility and applicability of the results of a network meta-analysis, and help make decision makers aware of the subtleties involved in the analysis of networks of randomized trial evidence. It is anticipated that user feedback will permit periodic evaluation and modification of the questionnaire.     

Fast pathway ablation in a patient with PR prolongation

The classical form of typical atrioventricular node reentrant tachycardia (AVNRT) is a “slow-fast” pathways tachycardia, and the usual therapy is an ablation of the slow pathway since it carries a low risk of atrioventricular (AV) block. In patients with long PR interval and/or living on the anterograde slow pathway, an alternative technique is required. We report a case of a 42-year-old lady with idiopathic restrictive cardiomyopathy, persistent atrial fibrillation status post pulmonary vein isolation, and premature ventricular complex ablation with a systolic dysfunction, who presented with incessant slow narrow complex tachycardia of 110 bpm that appeared to be an AVNRT. Her baseline EKG revealed a first-degree AV block with a PR of 320 ms. EP study showed no evidence of anterograde fast pathway conduction. Given this fact, the decision was to attempt an ablation of the retrograde fast pathway. The fast pathway was mapped during tachycardia to its usual location into the anteroseptal region, then radiofrequency ablation in this location terminated tachycardia. After ablation, she continued to have her usual anterograde conduction through slow pathway and the tachycardia became uninducible. In special populations with prolonged PR interval or poor anterograde fast pathway conduction, fast pathway ablation is the required ablation for typical AVNRT.